Currently used small diameter synthetic vascular grafts are prone to high rates of failure related to thrombosis and neointimal hyperplasia. Biomimetic materials, based on the extracellular matrix (ECM) composition of native tissues, represent an attractive solution to address these complications. The inherent low thrombogenicity and cell signalling properties of elastin-like polypeptides (ELPs) make them a suitable option for these applications.
In this thesis, ELP surface modification has been achieved through the use of elastin
cross-linking peptide bioactive fluorinated surface modifiers (ECP-BFSMs). The synthesis of these low molecular weight fluorinated additives was described and their subsequent blending with a base polycarbonate-urethane (PCNU) was shown to successfully enrich the surface to allow for ELP surface cross-linking. The kinetic surface migration of fluorescent ECP-BFSMs was studied over a 2 week casting period by two-photon confocal microscopy. Contact angle and x-ray photoelectron spectroscopy (XPS) confirmed the surface localization of the ECP-BFSMs.
Changes in contact angle and XPS spectrums following ELP surface cross-linking confirmed the success of the surface modification approach.
The novel ELP surface modified materials were demonstrated to inhibit fibrinogen
surface adsorption and platelet adhesion under physiological flow conditions and inhibit bulk platelet activation following blood-material contact. Moreover, these ELP modified surfaces were shown to promote increased endothelial and smooth muscle cell adhesion, spreading and retention over a 7 day culture period relative to their non-ELP analogs. Endothelial and smooth muscle cells seeded on the elastin-like materials were shown to express endothelial nitric oxide
synthase (eNOS) and smooth muscle myosin heavy chain (SM-MHC) cell specific phenotypic
markers, respectively. Furthermore, competitive inhibition experiments revealed that initial smooth muscle cell adhesion to ELP surface modified materials was mediated through elastin-laminin cell surface receptors binding to VGVAPG peptide sequences on the ELP molecules.
Hence, these materials may have broad applicability in cardiovascular applications, from blood contacting materials to scaffold structures for vascular graft tissue engineering. Furthermore, this surface modifying additive approach represents a versatile technique that can be custom tailored for various biomimetic applications to generate stable bioactive ECM-like surfaces retained onto
a relatively inert fluorinated background.
| Identifer | oai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/32200 |
| Date | 20 March 2012 |
| Creators | Blit, Patrick |
| Contributors | Santerre, J. Paul, Woodhouse, Kimberly A. |
| Source Sets | University of Toronto |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis, Image |
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